The Bordetella pertussis Type III Secretion System Tip Complex Protein Bsp22 Is Not a Protective Antigen and Fails To Elicit Serum Antibody Responses during Infection of Humans and Mice

Abstract

bThe type III secretion system (T3SS) of pathogenic bordetellae employs a self-associating tip complex protein Bsp22. This protein is immunogenic during infections by Bordetella bronchiseptica and could be used as a protective antigen to immunize mice against B. bronchiseptica challenge. Since low-passage clinical isolates of the human pathogen Bordetella pertussis produce a highly homologous Bsp22 protein (97% homology), we examined its vaccine and diagnostic potential. No Bsp22-specific antibodies were, however, detected in serum samples from 36 patients with clinically and serologically confirmed whooping cough disease (pertussis syndrome). Moreover, although the induction of Bsp22 secretion by the laboratory-adapted 18323 strain in the course of mice lung infection was observed, the B. pertussis 18323-infected mice did not mount any detectable serum antibody response against Bsp22. Furthermore, immunization with recombinant Bsp22 protein yielded induction of high Bsp22-specific serum antibody titers but did not protect mice against an intranasal challenge with B. pertussis 18323. Unlike for B. bronchiseptica, hence, the Bsp22 protein is nonimmunogenic, and/or the serum antibody response to it is suppressed, during B. pertussis infections of humans and mice.

Evaluation of Adenylate Cyclase Toxoid Antigen in Acellular Pertussis Vaccines by Using a Bordetella pertussis Challenge Model in Mice

“…An additional key aspect to consider is the potential endotoxin contamination in recombinant ACT preparations. Villarino Romero et al used recombinant ACT but did not observe the same bacterial clearance as Betsou et al (19,31). ACT used by Cheung et al was highly purified of endotoxin (21), as was the RTX that we used in this study (9).…”

“…Immunization with RTX alone does not enhance clearance of B. pertussis in CD-1 mice. ACT plays a key role in the pathogenesis of B. pertussis, and many studies have shown that both native and recombinant ACTs can be adjuvants and/or antigens for protection against pertussis in murine challenge studies (17)(18)(19)(20)(27)(28)(29)(30)(31). In this study, we aimed to systematically evaluate the RTX antigen (toxoid version of ACT, residues 751 to 1706) for inclusion into the acellular pertussis vaccine.…”

Bordetella pertussis pathogenesis: current and future challenges

“…In mouse models, ACT-deficient bacteria are cleared faster than wild-type bacteria, and studies with immunodeficient and neutropenic mice suggest that ACT has a crucial role in enabling bacteria to resist neutrophil-mediated clearance 72, 73 . These data, in addition to the fact that ACT is one of the few virulence factors that is conserved and produced by all pathogenic Bordetella species 5 , suggest that ACT has the potential to be an effective antigen in future vaccine formulations 74 .…”

Comparison of the Whole Cell Proteome and Secretome of Epidemic Bordetella pertussis Strains From the 2008–2012 Australian Epidemic Under Sulfate-Modulating Conditions

“…Several T3SS proteins were found to be significantly downregulated in this study including Bsp22, BopN, BopD, and BteA. Bsp22 forms the T3SS tip complex, while BopD is a translocase for the T3SS effectors BteA and BopN ( Fennelly et al, 2008 ; Nagamatsu et al, 2009 ; Romero et al, 2013 ). Bsp22, BopN, and BopD were also previously found to be downregulated in the secretome in non-modulation conditions ( Luu et al, 2018 ).…”